This invention relates to solid compositions of biocidal compounds that provide controlled release of the biocidal compounds, in particular, the controlled release of certain water-insoluble 3-isothiazolone compounds.
The ability to control the release of 3-isothiazolone compounds to a locus to be protected is important in the field of biologically active compounds, especially in the field of microbicides and marine antifouling agents. Typically, when a 3-isothiazolone compound is added to a locus to be protected, the compound is rapidly released, whether or not it is needed. Controlled release compositions deliver the 3-isothiazolone compound in a manner that more closely matches the need for the compound, that is, only the amount of the 3-isothiazolone compound actually needed is released into the locus to be protected. Controlled release offers the advantages of reduced cost, lowered toxicity and increased efficiency.
Solid formulations of 3-isothiazolone compounds are a useful method of delivering 3-isothiazolone compounds to a locus to be protected. Solid formulations also offer the advantage of safening the 3-isothiazolone compound by reducing the possibility of human exposure. For example, solid compositions eliminate the splash hazard that is common with liquid compositions.
Various solid compositions of 3-isothiazolone compounds are known. Such compositions include encapsulation of the 3-isothiazolone compound, adsorption of the 3-isothiazolone compound on an inert carrier such as silica gel, and clathration of the 3-isothiazolone compound. However, such solid compositions do not always provide controlled release of the 3-isothiazolone compounds. For example, solid compositions where the 3-isothiazolone compound is adsorbed on an inert solid carrier usually do not control the release of the 3-isothiazolone compound. Typically, once such a solid composition is added to a locus to be protected, the 3-isothiazolone compound is rapidly released. Thus, any safening of the 3-isothiazolone compound provided by the solid composition is lost once the composition is added to the locus.
For example, EP 106563 A discloses microbicidal compositions having a water-soluble microbicide admixed with an inert, finely-divided, water-insoluble solid carrier, such as clays, charcoal, inorganic silicates and silicas. These compositions do not provide controlled release of the 3-isothiazolone compounds. The compounds release into the locus by dissolution, and therefore, their release is controlled by the dissolution rate of the particular 3-isothiazolone compound. Similarly, U.S. Pat. No. 4,505,889 discloses microbicidal compositions having microbicide with low water-solubility admixed with an inert, finely-divided, water-insoluble solid carrier, such as clays, inorganic silicates and silicas. JP 63-35504 discloses controlled release sulfonylurea herbicide granules containing a mixture of activated carbon, paraffin wax and mineral based carrier, such as clay or diatomaceous earth. JP 59-227802 discloses an insecticidal resin composition containing an insecticide, a natural or synthetic resin (such as wax, polyethylene or polypropylene) and a porous substance (such as zeolites or activated carbon) to retain the insecticide. WO 96/38039 discloses controlled release pesticide compositions containing activated carbon and adsorbed pesticides, such as insecticides, herbicides or fungicides.
The problem addressed by the present invention is to provide solid compositions of 3-isothiazolone compounds that are safer to handle and provide controlled release of 3-isothiazolone compounds once the composition is added to a locus to be protected.
The present invention provides a solid composition comprising a 3-isothiazolone compound having low water solubility and a carbon-based adsorbent, wherein the composition provides controlled release of the 3-isothiazolone compound.
In a preferred embodiment, the invention provides a solid composition wherein the 3-isothiazolone compound is selected from one or more of 2-n-octyl-3-isothiazolone, 4,5-dichloro-2-n-octyl-3-isothiazolone, 4,5-dichloro-2-benzyl-3-isothiazolone and 2-benzyl-3-isothiazolone.
In another aspect, the present invention provides a method for controlling the growth of bacteria, fungi, algae and marine fouling organisms comprising introducing to a locus to be protected the solid composition described above. In particular the invention provides a method for controlling growth of the aforementioned organisms wherein the locus to be protected is selected from one or more of paints, coatings and marine structures.
We have discovered that solid compositions useful for providing the controlled release of 3-isothiazolone compounds can be prepared by combining selected 3-isothiazolone compounds having low water solubility with a carbon-based adsorbent. In particular, we have discovered that specific 3-isothiazolones combined in specific relative proportions with carbon-based adsorbents unexpectedly provides the controlled release compositions of the present invention.
As used throughout the specification, the following terms shall have the following meanings, unless the context clearly indicates otherwise. xe2x80x9cMicrobicidexe2x80x9d refers to a compound capable of inhibiting the growth of or controlling the growth of microorganisms in a locus. The term xe2x80x9clocusxe2x80x9d does not include pharmaceutical or veterinary applications. The term xe2x80x9cmicroorganismxe2x80x9d includes, for example, fungi, bacteria and algae. xe2x80x9cMarine antifouling agentxe2x80x9d includes algaecides and molluscicides. xe2x80x9cMarine antifouling activityxe2x80x9d is intended to include the elimination of and inhibition of growth of marine organisms. Marine organisms controlled by marine antifouling agents suitable for use in this invention include both hard and soft fouling organisms. Generally speaking, the term xe2x80x9csoft fouling organismsxe2x80x9d refers to plants and invertebrates, such as slime, algae, kelp, soft corals, tunicates, hydroids, sponges and anemones; and the term xe2x80x9chard fouling organismsxe2x80x9d refers to invertebrates having some type of hard outer shell, such as barnacles, tubeworms and molluscs.
As used herein, the term xe2x80x9clow water solubility,xe2x80x9d as applied to the 3-isothiazolones, means that the 3-isothiazolone is characterized by having a water solubility of less 1000 ppm (0.1%), preferably less than 500 ppm (0.05%) and more preferably less than 100 ppm (0.01%).
Unless otherwise specified, ranges listed are to be read as inclusive and combinable, temperatures are in degrees centigrade (xc2x0 C.) and references to percentages (%) are by weight. As used throughout this specification, the following abbreviations are applied: g=grams, mL=milliliter, ppm=parts per million (weight/weight) and mm=millimeter.
Suitable 3-isothiazolones useful in the present invention are those isothiazolones having low water solubility and are represented by the formula: 
wherein:
Y is an unsubstituted or substituted (C7-C18)alkyl group, an unsubstituted or substituted (C7-C18)alkenyl or alkynyl group, an unsubstituted or substituted (C7-C12)cycloalkyl group, an unsubstituted or substituted (C7-C10)aralkyl group, or a substituted (C7-C10)aryl group;
R and R1 are independently hydrogen, halogen or (C1-C4)alkyl groups; or
R and R1 can be taken together with the Cxe2x95x90C double bond of the isothiazolone ring to form an unsubstituted or substituted benzene ring.
By a xe2x80x9csubstituted alkyl groupxe2x80x9d is meant an alkyl group having one or more of its hydrogens replaced by another substituent group; examples include hydroxyalkyl, haloalkyl and alkylamino. By a xe2x80x9csubstituted aralkyl groupxe2x80x9d is meant an aralkyl group having one or more of its hydrogens on either the aryl ring or the alkyl chain replaced by another substituent group; examples include halo, (C1-C4)alkyl, halo-(C1-C4)alkoxy and (C1-C4)alkoxy. By a xe2x80x9csubstituted aryl groupxe2x80x9d is meant an aryl group, such as phenyl, naphthyl or pyridyl groups, having one or more of its hydrogens on the aryl ring replaced by another substituent group; examples include halo, nitro, (C1-C4)alkyl, halo-(C1-C4)alkoxy and (C1-C4)alkoxy.
Suitable 3-isothiazolone compounds include, for example, 2-n-octyl-3-isothiazolone, 4,5-dichloro-2-n-octyl-3-isothiazolone, 4,5-dichloro-2-benzyl-3-isothiazolone, 2-benzyl-3-isothiazolone and 2-haloalkoxyaryl-3-isothiazolones (such as 2-(4-trifluoromethoxyphenyl)-3-isothiazolone, 2-(4-trifluoromethoxyphenyl)-5-chloro-3-isothiazolone and 2-(4-trifluoromethoxyphenyl)-4,5-dichloro-3-isothiazolone). Preferably, the 3-isothiazolone is selected from one or more of 2-n-octyl-3-isothiazolone and 4,5-dichloro-2-n-octyl-3-isothiazolone.
When the 3-isothiazolone compound is a solid, the compositions of the invention may be prepared by mixing the 3-isothiazolone compound, as a melt or as a solution, with the carbon-based adsorbent. When the 3-isothiazolone compound is a liquid, the 3-isothiazolone compound may be mixed xe2x80x9cas isxe2x80x9d with the carbon-based adsorbent, or mixed as a solution with the carbon-based adsorbent. Suitable solvents for the 3-isothiazolone compound are any which dissolve the compound, do not destabilize it and do not react with the carbon-based adsorbent. Suitable solvents include alcohols, such as methanol, ethanol and propanol; esters, such as ethyl acetate and butyl acetate; ketones, such as acetone and methyl iso-butyl ketone; and nitriles, such as acetonitrile. Preferred solvents are (C1-C4)alcohols.
The total amount of 3-isothiazolone compound in the composition is 0.1 to 95%, based on the combined weight of the carbon-based adsorbent and the 3-isothiazolone compound. Preferably, the total amount of 3-isothiazolone compound is 1 to 50% and more preferably 5 to 30%. Thus, the weight ratio of 3-isothiazolone compound to carbon-based adsorbent in the compositions is generally from 0.1:99.9 to 95:5, preferably from 1:99 to 50:50 and more preferably from 5:95 to 30:70.
Suitable carbon-based adsorbents include, for example, carbons such as those derived from coal, wood, coconut shells, lignin or animal bones; carbon blacks such as those derived from gas phase pyrolysis of hydrocarbons; natural or synthetic graphites or graphite whiskers; cokes such as those obtained from the destructive distillation of bituminous coal, petroleum and coal-tar pitch; high surface area activated carbons; and pyrolyzed carbonaceous adsorbents prepared by pyrolysis of resinous polymers (such as Ambersorb(trademark) carbonaceous adsorbents, available from Rohm and Haas Company, Philadelphia, Pa.; see Carbonaceous Adsorbents for the Treatment of Ground and Surface Waters, J. W. Neely and E. G. Isacoff, Vol 21 of Pollution Engineering and Technology Series, Marcel Dekker, Inc., New York, N.Y., pp 41-78 (1982), for further general and specific details on pyrolyzed carbonaceous adsorbents and their method of preparation). Preferably the carbon-based adsorbent is selected from one or more of activated carbon and pyrolyzed carbonaceous adsorbent.
Particularly preferred are high surface area xe2x80x9cactivatedxe2x80x9d carbons, such as those prepared by direct chemical activation. Petroleum Derived Carbons (by T. M. O""Grady and A. N. Wennerberg), American Chemical Society Symposium Series, Vol. 303, J. D. Bacha et al., eds., American Chemical Society Publications, Washington, D.C., (1986), may be consulted for further general and specific details on these activated carbons and their method of preparation.
The carbon-based adsorbents are typically particulate materials having an average particle size of 0.01 to 5 mm (10 to 5000 microns), preferably from 0.02 to 2 mm and more preferably from 0.1 (less than 100 mesh) to 1 mm (about 18 mesh). When relatively large particle sized carbon-based adsorbents are used, the average particle size typically ranges from 0.5 to 3 mm, preferably from 1 to 2 mm (greater than 18 mesh) and more preferably from 1.5 to 2 mm. When smaller particle sized carbon-based adsorbents are used, the average particle size typically ranges from 0.02 to 0.3 mm and preferably from 0.03 to 0.15 mm (30 to 150 microns, less than 100 mesh).
More than one 3-isothiazolone compound may be used in the compositions of the present invention as long as the compounds do not react with, or otherwise destabilize, each other and are compatible with the carbon-based adsorbent. This has the advantage of safening multiple 3-isothiazolone compounds which may provide a broader spectrum of control than one compound used alone.
The compositions of the present invention are useful wherever the low water solubility 3-isothiazolone compound would be useful. The compositions are suitable for use in any locus requiring protection from microorganisms. Suitable loci include, for example, cooling towers; air washers; mineral slurries; pulp and paper processing fluids; paper coatings; swimming pools; spas; adhesives; caulks; mastics; sealants; agriculture adjuvant preservation; construction products; cosmetics and toiletries; shampoos; disinfectants and antiseptics; formulated industrial and consumer products; soaps; laundry rinse waters; leather and leather products; wood products, including lumber, timber, fiberboard, plywood, and wood composites; plastics; lubricants; hydraulic fluids; medical devices; metalworking fluids; emulsions and dispersions; paints, including marine paints; varnishes, including marine varnishes; latexes; odor control fluids; coatings, including marine coatings; petroleum processing fluids; fuel; oil field fluids; photographic chemicals; printing fluids; sanitizers; detergents; textiles; textile products; and marine structures. Preferably the locus to be protected is selected from one or more of paints, coatings and marine structures.
The compositions of the present invention can either be added directly to the locus to be protected or added as a composition further comprising a suitable carrier. Suitable carriers include, for example, water, acetonitrile, ethyl acetate, butyl acetate, toluene, xylene, methanol, ethanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl isoamyl ketone, ethylene glycol, diethylene glycol, propylene glycol and dipropylene glycol. When the compositions of the present invention are used in marine antifoulant formulations, the compositions preferably incorporate an optional carrier selected from one or more of water, xylene, methyl isobutyl ketone and methyl isoamyl ketone. The compositions may also be formulated as microemulsions, microemulsifiable concentrates, emulsions, emulsifiable concentrates, pastes, or may be encapsulated. The particular formulation will depend upon the locus to be protected and the particular low water solubility 3-isothiazolone used. The preparation of these formulations are by well known, standard methods.
The amount of the compositions of the invention necessary to control or inhibit the growth of microorganisms depends upon the locus to be protected, but is typically sufficient if it provides 0.1 to 5000 ppm of 3-isothiazolone at the locus to be protected. 3-Isothiazolones are often used in loci that require further dilution. In a locus such as a paint, which is not further diluted, the amount of the compositions of the invention necessary to control microorganism growth are sufficient if they provide generally 200 to 5000 ppm of the 3-isothiazolone.
When the low water solubility 3-isothiazolone compound of the present invention is used in a marine antifoulant formulation, that is, as a marine antifouling agent, the compositions of the present invention can be used to inhibit the growth of marine organisms by application of the compositions onto or into a marine structure. Depending upon the particular marine structure to be protected, the compositions of the present invention can be directly incorporated into the marine structure, applied directly to the marine structure, or incorporated into a coating which is then applied to the marine structure.
Suitable marine structures include, but are not limited to: boats, ships, oil platforms, piers, pilings, docks, elastomeric rubbers, and fish nets. The compositions of the present invention are typically directly incorporated into structures such as elastomeric rubber or fish net fibers during manufacture. Direct application of the compositions of the invention is typically made to structures such as fish nets or wood pilings. The compositions of the invention can also be incorporated into a marine coating, such as a marine paint or varnish.
Optionally, the controlled release compositions of the present invention may include other marine antifouling agents in addition to the low water solubility 3-isothiazolones. Suitable optional marine antifouling agents useful in the present invention include, for example, manganese ethylenebisdithiocarbamate, zinc ethylenebisdithiocarbamate, zinc dimethyl dithiocarbamate, 2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine, 2,4,5,6-tetrachloroisophthalonitrile, 3-(3,4-dichloro-phenyl)-1,1-dimethyl urea, zinc ethylenebisdithiocarbamate, copper thiocyanate, N-(fluorodichloromethylthio)phthalimide, N,N-dimethyl-Nxe2x80x2-phenyl-Nxe2x80x2-fluorodichloromethylthiosulfamide, zinc 2-pyridinethiol-1-oxide, copper 2-pyridinethiol-1-oxide, tetramethylthiuram disulfide, 2,4,6-trichlorophenylmaleimide, 2,3,5,6-tetrachloro-4-(methylsulfonyl)pyridine, 3-iodo-2-propynylbutylcarbamate, diiodomethyl p-tolyl sulfone, bis dimethyl dithiocarbamoyl zinc, phenyl (bispyridil) bismuth dichloride, 2-(4-thiazolyl)-benzimidazole, pyridine triphenyl borane, phenylamides and halopropargyl compounds.
Additional optional compounds that may be incorporated into the solid controlled release compositions of the present invention include, for example, 2-(C1-C6)alkyl-3-isothiazolones (such as 2-methyl-3-isothiazolone and 5-chloro-2-methyl-3-isothiazolone) and 2-phenyl-3-isothiazolone.
When the solid compositions of the present invention are used in marine antifoulant formulations, the amount of the compositions necessary to inhibit or prevent the growth of marine organisms is typically sufficient if it provides from 0.1 to 30%, preferably from 0.5 to 20% and more preferably from 1 to 10%, of the low water solubility 3-isothiazolone, based on the weight of the structure to be protected or based on the weight of the coating to be applied (whether directly incorporated into or directly applied onto a structure). In the case of a marine antifouling paint, the concentration of low water solubility 3-isothiazolone is typically from 0.1 to 15%, preferably from 0.2 to 5% and more preferably from 0.5 to 3%, based on total weight of the paint formulation.
In general, the compositions of the present invention may be used by first forming the solid composition (combining the low water solubility 3-isothiazolone with a carbon-based adsorbent), followed by addition of the solid composition to various loci (as previously described).
Alternatively, the present invention may be practiced, in particular for controlling the growth of bacteria, fungi, algae and marine fouling organisms, by introducing to any locus to be protected: (a) a carbon-based adsorbent, and (b) a low water solubility 3-isothiazolone compound as represented by formula I. For example, when the locus is a solvent-based paint, such as a marine antifouling paint, the paint formulation may be prepared by adding the carbon-based adsorbent and 3-isothiazolone separately, and in any order, to the base paint formulation.
Direct applications of the compositions of the present invention may be by any conventional means, such as dipping, spraying or coating. Fish nets, for example, may be also protected by dipping the fish nets into a composition comprising the compositions of the invention and a carrier or by spraying the fish nets with the composition.
Structures such as wood pilings and fish nets may be protected by directly incorporating the compositions of the invention into the structure. For example, a composition of the invention further comprising a carrier may be applied to wood used for pilings by means of pressure treatment or vacuum impregnation. These compositions may also be incorporated into a fish net fiber during manufacture.
Marine coatings comprise a binder and solvent and optionally other ingredients. The solvent may be either organic solvent or water. The compositions of the invention are suitable for use in both solvent and water based marine coatings. Solvent based marine coatings are preferred.
Any conventional binder may be utilized in the marine antifouling coating incorporating the compositions of the invention. Suitable binders include, for example, polyvinyl chloride in a solvent based system, chlorinated rubber in a solvent based system, acrylic resins in solvent based or aqueous systems, vinyl chloride-vinyl acetate copolymer systems as aqueous dispersions or solvent based systems, butadiene-styrene rubbers, butadiene-acrylonitrile rubbers, butadiene-styrene-acrylonitrile rubbers, drying oils such as linseed oil, asphalt, epoxies, siloxanes and silicones.
The marine coatings of the present invention may optionally contain one or more of the following: inorganic pigments, organic pigments or dyes, and natural resins, such as rosin. Water based coatings may also optionally contain: coalescents, dispersants, surface active agents, rheology modifiers or adhesion promoters. Solvent based coatings may also optionally contain extenders, plasticizers or rheology modifiers.
A typical marine coating comprises 2 to 20% binders, up to 15% rosins/modified rosins, 0.5 to 5% plasticizers, 0.1 to 2% antisettling agent, 5 to 60% solvent/diluent, up to 70% cuprous oxide, up to 30% pigments (other than cuprous oxide) and up to 15% marine antifouling agent (in this case, low water solubility 3-isothiazolone).
Marine coatings containing the compositions of the invention may be applied to a structure to be protected by any of a number of conventional means, such as, for example, spraying, rolling, brushing and dipping.